This invention is related to a novel polypeptide having mammalian growth factor activity and to methods for using it.
A variety of diffusible factors which stimulate the growth of cells in a hormone-like manner are generally called xe2x80x9cgrowth factorsxe2x80x9d. Growth factors are present in serum and have also been isolated from a variety of organs. They are protein molecules (or groups of such molecules) and in all known cases they interact with specific cell surface receptors to promote cellular growth and/or differentiation. Growth factors vary in their tissue specificity, i.e. some interact only with specific cell types, while others are active on a wider cell type range.
Among the best known groups of growth factors are: (1) platelet derived growth factor (PDGF), released from platelets; (2) epidermal growth factor (EGF); (3) hematopoietic growth factors (including interleukins 1, 2, and 3), required for growth and differentiation of lymphocytes, and colony stimulating factors (CSF), promoting growth and differentiation of hematopoietic stem cells; (4) angiogenic (literally xe2x80x9cblood-vessel-formingxe2x80x9d) growth factors, such as the fibroblast growth factors (FGF) believed to promote growth and organization of endothelial cells into new blood vessels; (5) a variety of growth factors released by tumor cells and falling into two groups: alpha and beta, corresponding to their chains.
The only well-characterized angiogenic factors are basic and acidic fibroblast growth factors (FGF); believed to be most important in vivo for endothelial cell growth.
It is known that the oncogene that is characteristic of simian sarcoma virus encodes the B chain of PDGF. However, none of the remaining growth factors mentioned above are produced by oncogenes. Nor do other known oncogenes produce growth factors.
Growth factors are believed to promote wound healing. For example, EGF present in saliva is believed to accelerate wound healing in mice. Schultz G. S et al (Science 232:350-352, 1986) report that transforming growth factor (TGF)-alpha and vaccinia virus growth factor (VGF), both of which are substantially homologous to EGF, accelerated epidermal wound healing in pigs when topically applied to second degree burns and were significantly more active than EGF.
Of the above-mentioned growth factors, the angiogenic growth factors would be particularly useful as wound healing agents because of their ability to promote the formation and growth of new blood vessels. Preliminary evidence indicates that the two known (sequenced) angiogenic growth factors, basic and acidic FGF (so named due to the total net charge on the molecules) may be of use as wound healing agents.
It is an object of the present invention to provide a growth factor useful as a wound healing agent in mammals.
It is another object of the present invention to provide a mammalian growth factor with a tissue specificity wider than either acidic or basic FGF.
Another object is to provide novel pharmaceutical formulations and methods for promoting wound healing.
These and other objects of the present invention will be apparent to those of ordinary skill in the art in light of the present description, accompanying claims and appended drawings.
The present inventors have unexpectedly discovered a single polypeptide which displays substantial homology to each of basic and acidic fibroblast growth factor, said polypeptide having growth factor activity and having an amino acid sequence consisting essentially of the amino acid sequence of the expression product of a fragment of an oncogene isolated from Kaposi""s sarcoma DNA. In another aspect, the present invention is directed to a DNA molecule coding for the above polypeptide.
In yet another aspect, the present invention is directed to methods for promoting the healing of mammalian wounds or burns comprising administering to a mammal in need of such treatment a healing-promoting effective amount of the above polypeptide and to pharmaceutical formulations comprising said polypeptide and a pharmaceutically acceptable carrier or diluent.